Glomerular expression of nephrin is decreased in acquired human nephrotic syndrome

Background. Nephrin recently has been identified as a putative adhesion molecule, expressed in the glomerulus, in which mutations cause congenital nephrotic syndrome of Finnish type. We sought to determine whether expression of nephrin is altered in human glomeruli in patients with acquired nephrotic syndrome. Methods. We performed PCR amplification of nephrin cDNA, using cDNA previously prepared from single human glomeruli plucked fresh from the surface of human renal biopsies. We had available four cases of nephrotic syndrome (one membranous, three minimal change) and six normal controls. PCR product quantitation was by gel densitometry, confirmed by enzyme-linked immunosorbent assay using a specific oligonucleotide probe. Results were corrected for reaction efficiency and glomerular cellularity by expression as a ratio to levels of the 'housekeeping gene' glyceraldehyde phosphate dehydrogenase. Results. Glomerular levels of nephrin mRNA are significantly decreased in cases of minimal change nephrotic syndrome. An apparent reduction was also seen in the single case of membranous nephropathy which was available for study. Conclusions. Abnormalities of nephrin expression appear to be associated with acquired as well as congenital causes of human nephrotic syndrome.